Many HIV cure studies are planned or expected. These studies often involve high or unknown risks, raising serious ethical challenges concerning (I) risk/benefit ratios, (II) informed consent, and (III) trust in investigators. Little empirical r philosophical research into these challenges is available. The proposed study will use modeling to assess objective risks from various HIV cure interventions, use surveys to assess patients' and investigators' risk ethical approval and willingness to partake in those studies, and use philosophical analysis to make related recommendations on the ethical conduct of HIV cure studies. Innovation: The proposed study is innovative in several ways: (a) It will apply CEPAC modeling, which has been validated in other contexts, to investigate the new area of HIV cure interventions; (b) It will use our ready access to the large ACTG network, which has successfully supported other surveys, for a large survey of patients and clinicians on something for which no survey currently exists-ethics and willingness to participate in risky HIV cure studies; (c) It is the first large study to thoroughly examine these philosophical challenges in HIV cure studies; (d) It will translate ethics insights from early phase cancer studies, other first-in-human studies and elsewhere into practical recommendations for ethical HIV cure research, to guide investigators, funders, and IRBs, honed with key stakeholders. Approach: We will first compile and catalogue conceivable responses to the ethical challenge of HIV cure studies. Some responses will be immediately screened out for obvious logical, practical, or ethical flaws (Filte A). Among remaining responses, we shall assess the risks of cure interventions comprising them (Aim 1). We shall also conduct surveys to check how much HIV patients and clinicians in 34 US-based ACTG sites are willing to partake in studies that involve similar risk levels, and how morally acceptable they would find such studies (Aim 2). Combined, Aims 1 and 2 will rule out some responses to the challenge as infeasible (Filter B). Then, we shall assess the ethics of remaining responses to the challenge (Filter C) and make recommendations on how to conduct HIV cure studies ethically (Aim 3). Our draft recommendations will be presented to HIV cure decision makers, IRB members, and other key stakeholders to obtain feedback and hone the recommendations. (Filter D). We propose the following aims: 1. Assess through modeling the risk from HIV cure study participation for various patient populations. 2. Empirically assess HIV investigators' and HIV patients' ethical evaluation and willingness to partake in HIV cure studies involving given risk levels. 3. Use these results, along with philosophical analysis, published ethics literature, feedback from our Board of Advisors, and feedback from key stakeholders, to form model ethical recommendations for HIV cure research.